Canine distemper virus strains circulating among North American dogs

Canine distemper virus (CDV) is a highly contagious virus that causes multisystemic disease in dogs. We received seven samples from dogs with CD from the United States during 2007. CDV isolates from these samples formed large, multinucleated syncytia in a Vero cell line expressing canine signaling lymphocyte activation molecule (SLAM). Based on the hemagglutinin gene sequences, the CDV isolates from three states (California, Missouri, and Oklahoma) formed two CDV genetic groups: group I (major; six of seven isolates) consisted of CDV isolates closely related to the European wildlife lineage of CDV, and group II (minor; one of seven isolates) was genetically related to the Arctic-like lineage of CDV. However, both CDV groups were genetically different from the current vaccine strains that belong to the American-1 lineage of the old (1930 to 1950) CDV isolates.     

Active CD4+ helper T cells directly stimulate CD8+ cytotoxic T lymphocyte responses in wild-type and MHC II gene knockout C57BL/6 mice and transgenic RIP-mOVA mice expressing islet beta-cell ovalbumin antigen leading to diabetes

CD4+ helper T (Th) cells play crucial role in priming, expansion and survival of CD8+ cytotoxic T lymphocytes (CTLs). However, how CD4+ Th cell's help is delivered to CD8+ T cells in vivo is still unclear. We previously demonstrated that CD4+ Th cells can acquire ovalbumin (OVA) peptide/major histocompatibility complex (pMHC I) and costimulatory CD80 by OVA-pulsed DC (DC(OVA)) stimulation, and then stimulate OVA-specific CD8+ CTL responses in C57BL/6 mice. In this study, we further investigated CD4+ Th cell's effect on stimulation of CD8 CTL responses in major histocompatibility complex (MHC II) gene knockout (KO) mice and transgenic rat insulin promoter (RIP)-mOVA mice with moderate expression of self OVA by using CD4+ Th cells or Th cells with various gene deficiency. We demonstrated that the in vitro DC(OVA)-activated CD4+ Th cells (3 x 10(6) cells/mouse) can directly stimulate OVA-specific CD8+ T-cell responses in wild-type C57BL/6 mice and MHC II gene KO mice lacking CD4+ T cells. A large amount of CD4+ Th cells (12 x 10(6) cells/mouse) can even overcome OVA-specific immune tolerance in transgenic RIP-mOVA mice, leading to CD8+ CTL-mediated mouse pancreatic islet destruction and diabetes. The stimulatory effect of CD4+ Th cells is mediated by its IL-2 secretion and CD40L and CD80 costimulations, and is specifically delivered to OVA-specific CD8+ T cells in vivo via its acquired pMHC I complexes. Therefore, the above elucidated principles for CD4+ Th cells will have substantial implications in autoimmunity and antitumor immunity, and regulatory T-cell-dependent immune suppression.     

Detection of membrane fluidity in submitochondrial particles of platelets and erythrocyte membranes from Mexican patients with Alzheimer disease by intramolecular excimer formation of 1,3 dipyrenylpropane

It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes. The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 +/- 0.008) than aged-matched control subjects (0.363 +/- 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged-matched controls: the fluorescent intensity ratios were 0.312 +/- 0.03 and 0.305 +/- 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged-matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.     

Crystalloid inclusions in brain macrophages and hemopoietic tissue in GFAP-IL3 mice resemble inclusions identified in multiple sclerosis

Crystalloid inclusions or "pole bodies" observed in brain macrophages in human demyelinating disease represent a morphological enigma. Similar inclusions were detected in brain macrophages from the GFAP-IL3 mouse, a transgenic murine model for macrophage mediated demyelination. Mice also showed inclusions in hematopoietic tissue. They appear to be related to phagocytosis and secretion, respectively, as evidenced by the fact that in phagocytosing cells they often merged with lysozomes and that affected cells showed empty channels open to the interstitium. Based on ultrastructural and immunolocalization studies using chaperonin-10, lysozyme, and cathepsin the authors suggest that these inclusions are consistent with phagocytosis-related secretory products. This study may provide insight into the nature and significance of similar macrophage inclusions recently identified in multiple sclerosis.     

Comparison of isolation media for recovery of Burkholderia cepacia complex from respiratory secretions of patients with cystic fibrosis

Burkholderia cepacia selective agar (BCSA) has previously been devised for isolation of B. cepacia from respiratory secretions of patients with cystic fibrosis and tested under research laboratory conditions. Here we describe a study in which BCSA, oxidation-fermentation polymyxin bacitracin lactose agar (OFPBL), and Pseudomonas cepacia agar (PCA) were compared in routine culture procedures for the ability to grow B. cepacia and inhibit other organisms. Three hundred twenty-eight specimens from 209 patients at two pediatric centers and 328 specimens from 109 adults were tested. Plates were inoculated, incubated, and read for quality and quantity of growth at 24, 48, and 72 h. Five (1.5%) specimens from 4 (1.9%) children and 75 (22.9%) specimens from 16 (14.7%) adults grew B. cepacia complex. At 24, 48, and 72 h, BCSA achieved 43, 93, and 100% detection, respectively; OFPBL achieved 26, 84, and 96%, respectively; and PCA achieved 33, 74, and 84% detection, respectively. Quality was assessed as pinpoint or good growth. At 24 h, most cultures growing B. cepacia complex had pinpoint colonies. By 48 and 72 h, 48 and 69% of B. cepacia complex cultures, respectively, had good growth on BCSA, while on OFPBL 19 and 30%, respectively, had good growth and on PCA 11 and 18%, respectively, had good growth. BCSA was superior to OFPBL and PCA in suppressing organisms other than B. cepacia complex; 40 non-B. cepacia complex organisms were isolated from BCSA, 263 were isolated from OFPBL, and 116 were isolated from PCA. We conclude that BCSA is superior to OFPBL and PCA in its ability to support the growth of B. cepacia complex and to suppress other respiratory organisms.     

Anti-inflammatory actions of interleukin-13: suppression of tumor necrosis factor-alpha and antigen-induced leukocyte accumulation in the guinea pig lung

The Th2 cytokine interleukin (IL)-13 is believed to play an important role in the development of allergy, although it has also been ascribed anti-inflammatory roles in several experimental models. In this study, we have examined the effects of human recombinant IL-13 on eosinophilic lung inflammation in the guinea pig. IL-13 (1 to 100 ng, given by intratracheal instillation) did not elicit airway eosinophil recruitment. A pronounced accumulation of eosinophils, as well as monocyte/macrophages, was elicited by intratracheal instillation of guinea pig tumor necrosis factor alpha (gpTNF-alpha). Intratracheal administration of IL-13 (1 to 100 ng) given immediately prior to exposure to gpTNF-alpha resulted in a dose-related suppression of eosinophil and monocyte/macrophage accumulation in the airways, as assessed by bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in whole-lung homogenates. IL-13 treatment also reduced BAL fluid (BALF) leukocyte accumulation induced by subsequent aerosol antigen challenge of sensitized guinea pigs. Antigen challenge also resulted in elevated levels of immunoreactive eotaxin and eosinophil-stimulating activity in BALF, although only the latter was reduced significantly by IL-13 instillation prior to challenge. In contrast to the suppressive effects of IL-13, instillation of human recombinant IL-4 (100 ng) alone elicited an increase in BALF monocyte/macrophage numbers, and IL-4 was unable to inhibit gpTNF-alpha-induced leukocyte accumulation. Hence, IL-13 (but not human IL-4) exhibits an anti-inflammatory action in the airways of gpTNF-alpha- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulating activity in the airways.     

Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) infection in men receiving treatment for HIV-1 infection

OBJECTIVE: To determine the prevalence of human herpesvirus 8 (HHV-8) infection in men treated for HIV-1 infection in Denver, Colorado. DESIGN: Cross-sectional analysis METHODS: Blood samples were obtained from 216 HIV-1-infected men. Antibody to latency-associated nuclear antigen (LANA) was detected by an immunofluorescent assay and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC) was detected by polymerase chain reaction amplification. RESULTS: Among HIV-1-infected men who did not have Kaposi's sarcoma (KS), prevalence of HHV-8 infection was 46% (95% confidence interval [CI], 0.39-0.52). LANA seropositivity was common both among subjects with KS and subjects without KS (69% versus 42%; p = .06), but detection of HHV-8 DNA in peripheral blood was strongly associated with a diagnosis of KS (44% versus 10%; p = .001). In a univariate analysis of study subjects without KS, neither the odds of LANA seropositivity nor detection of HHV-8 DNA in PBMC was significant for CD4+ lymphocyte count, HIV-1 virus load, the use of three drug antiretroviral regimens or the prior occurrence of non-KS AIDS-related conditions. CONCLUSION: Although antibodies to HHV-8 are common among HIV-1-infected men, detection of HHV-8 DNA in PBMC is uncommon and is associated with a diagnosis of Kaposi's sarcoma.     

Cutaneous Scedosporium apiospermum infection in an immunocompromised patient

Scedosporium apiospermum infection occurred in the left forearm of a patient who was taking oral prednisolone for pulmonary fibrosis. The infection appeared to follow a scratch from a blackcurrant bush. This is the first reported case in the United Kingdom of a cutaneous infection from Scedosporium apiospermum in an immunocompromised patient.     

Decreased superoxide production, degranulation, tumor necrosis factor alpha secretion, and CD11b/CD18 receptor expression by adherent monocytes from preterm infants.

Preterm infants have an increased incidence of infection, which is principally due to deficiencies in neonatal host defense mechanisms. Monocyte adherence is important in localizing cells at sites of infection and is associated with enhanced antimicrobial functions. We isolated cord blood monocytes from preterm and full-term infants to study their adhesion and immune functions, including superoxide (O2-) generation, degranulation, and cytokine secretion and their adhesion receptors. O2- production and degranulation were significantly diminished, by 28 and 37%, respectively, in adherent monocytes from preterm infants compared to full-term infants (P < 0. 05); however, these differences were not seen in freshly isolated cells. We also observed a significant decrease of 35% in tumor necrosis factor alpha secretion by lipopolysaccharide-stimulated adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, this difference was not observed in interleukin-1beta or interleukin-6 production by the monocytes. The cell surface expression of the CD11b/CD18 adhesion receptor subunits was significantly decreased (by 60 and 52%, respectively) in monocytes from preterm infants compared to full-term infants (P < 0. 01). The cascade of the immune response to infection involves monocyte upregulation and adherence via CD11b/CD18 receptors followed by cell activation and the release of cytokines and bactericidal products. We speculate that monocyte adherence factors may be important in the modulation of immune responses in preterm infants.